ALX Oncology has announced the initiation of a Phase 2 investigator-sponsored trial evaluating evorpacept, a next-generation CD47 blocker, in combination with liposomal doxorubicin and pembrolizumab (KEYTRUDA®) for patients with recurrent platinum-resistant ovarian cancer. The trial is being conducted at the UPMC Hillman Cancer Center.
This open-label, single-arm Phase 2 clinical trial (NCT05467670) is led by Dr. Haider Mahdi from the University of Pittsburgh and UPMC Magee-Womens Research Institute. Merck will supply KEYTRUDA® for the study. The primary aim is to assess the efficacy and safety of this novel combination in a patient population with limited treatment options.
Rationale for the Combination Therapy
Dr. Mahdi stated, "Ovarian cancer patients who develop platinum-resistant disease have poor prognosis and are in desperate need of new treatment options that are safe and effective." He further explained the mechanistic rationale, noting that CD47 blockade complements chemotherapeutic agents and immune checkpoint inhibitors. The investigators anticipate that the combination of evorpacept, liposomal doxorubicin, and pembrolizumab may lead to improved efficacy and a more favorable benefit-risk profile.
Ovarian Cancer Statistics and Unmet Needs
Ovarian cancer is a significant cause of cancer-related deaths among women. In the United States, it ranks as the fifth leading cause, with nearly 13,000 deaths in 2022. While there have been advances in treating newly diagnosed ovarian cancer, advanced ovarian cancer remains largely incurable, with 80% of patients experiencing disease recurrence.
ALX Oncology's Broader Clinical Development Program
ALX Oncology is also evaluating evorpacept in combination with zanidatamab in HER2-positive and HER2-low metastatic breast cancer. Results from a Phase 1b/2 trial will be presented at the San Antonio Breast Cancer Symposium (SABCS) in December 2024. The Phase 1b/2 clinical trial (NCT05027139) is a two-part, open-label, multicenter study evaluating evorpacept in combination with zanidatamab as a novel treatment for patients with HER2-expressing breast cancer and other cancers.
Evorpacept, ALX Oncology's lead product candidate, is a next-generation CD47 blocking therapeutic designed to bridge the innate and adaptive immune systems. It combines a high-affinity CD47 binding domain with an inactivated Fc domain. Clinical trials have demonstrated promising responses across various hematologic and solid malignancies when evorpacept is combined with other anti-cancer agents.
